GPR39 (Zinc Receptor) Knockout Mice Exhibit Depression-Like Behavior and CREB/BDNF Down-Regulation in the Hippocampus

Background:Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors.Methods:In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail suspe...

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Veröffentlicht in:The international journal of neuropsychopharmacology Jg. 18; H. 3; S. 1 - 8
Hauptverfasser: Młyniec, Katarzyna, Budziszewska, Bogusława, Holst, Birgitte, Ostachowicz, Beata, Nowak, Gabriel
Format: Journal Article
Sprache:Englisch
Veröffentlicht: US Oxford University Press 01.02.2015
Schlagworte:
Animals
Anxiety
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - metabolism
Corticosterone - blood
CREB-Binding Protein - metabolism
Dark Adaptation - genetics
Depression - genetics
Depression - metabolism
Depression - pathology
Disease Models, Animal
Down-Regulation - genetics
Hindlimb Suspension
Hippocampus - metabolism
Hypothalamus
Immobility Response, Tonic - physiology
Kinases
Male
Mental depression
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity - genetics
Proteins
Receptor, trkB - metabolism
Receptors, G-Protein-Coupled - deficiency
Receptors, G-Protein-Coupled - genetics
Swimming - psychology
Time Factors
Zinc - metabolism
GPR39
HPA axis
CREB
depression
zinc receptor
ISSN:1461-1457, 1469-5111, 1469-5111
Online-Zugang:Volltext
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Zusammenfassung:Background:Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors.Methods:In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail suspension test, and light/dark test. We also investigated whether lack of GPR39 would change levels of cAMP response element-binding protein (CREB),brain-derived neurotrophic factor (BDNF) and tropomyosin related kinase B (TrkB) protein in the hippocampus and frontal cortex of GPR39 knockout mice subjected to the forced swim test, as measured by Western-blot analysis.Results:In this study, GPR39 knockout mice showed an increased immobility time in both the forced swim test and tail suspension test, indicating depressive-like behavior and displayed anxiety-like phenotype. GPR39 knockout mice had lower CREB and BDNF levels in the hippocampus, but not in the frontal cortex, which indicates region specificity for the impaired CREB/BDNF pathway (which is important in antidepressant response) in the absence of GPR39. There were no changes in TrkB protein in either structure. In the present study, we also investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex.Conclusions:There were no changes in the GPR39 knockout mice in comparison with the wild-type control mice, which does not support a role of GPR39 in hypothalamus-pituitary-adrenal axis regulation. The results of this study indicate the involvement of the GPR39 Zn2+-sensing receptor in the pathophysiology of depression with component of anxiety.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1461-1457
1469-5111
1469-5111
DOI:10.1093/ijnp/pyu002